..The past five years have witnessed important insights into osteoclast formation and function. Many of these discoveries have been made through genetic experiments that involved the rare hereditary disorder osteopetrosis...

Dynamic changes in the osteoclast cytoskeleton in response to growth factors and cell attachment are controlled by beta3 integrin

..Furthermore, this same add-back approach identifies important roles for Tyr-697 and Tyr-721 in collaborating with Tyr-559 to recruit a multimeric signaling complex that can transduce signals from c-Fms to the actin cytoskeleton...

..Using specific small molecule inhibitors we find that a combination of the Src family kinase, phosphatidylinositol 3-kinase/Akt, phospholipase C, and ERK pathways mediates macrophage proliferation in response to M-CSF...

..Moreover, we provide genetic and biochemical evidence for the role of Syk tyrosine kinase as a crucial upstream regulator of Vav3 in osteoclasts. Thus, Vav3 is a potential new target for antiosteoporosis therapy...

..Such inhibition requires Zap70 kinase activity, as it is abolished by mutation of the Zap70 kinase domain. Thus, while the kinase domain of Syk is uniquely required for OC function that of Zap70 inhibits it...

Tyrosines 559 and 807 in the cytoplasmic tail of the macrophage colony-stimulating factor receptor play distinct roles in osteoclast differentiation and function

..Thus, we have identified specific tyrosine residues in the cytoplasmic tail of c-Fms that are critical for transmitting M-CSF-initiated signals individually required for OC formation or function, respectively...

..Estrogen deprivation, therefore, promotes RANKL expression and bone resorption in association with upregulation of the IL-17 effector, Act1, supporting the concept that post-menopausal osteoporosis is a disorder of innate immunity...

..Signals from alphavbeta3 and/or c-Fms activate Syk and Vav3, originally defined by their function in lymphoid cells. Genetic depletion of either protein generates a strong bone phenotype, underscoring the promise of osteoimmunobiology...

..Thus, Rac1 and Rac2 are mutually compensatory. Unlike Cdc42 deficiency, their combined absence does not impact upon differentiation but promotes severe osteopetrosis by dysregulating the osteoclast cytoskeleton...

..Thus, NF-kappaB appears to be the centerpiece of inflammatory-osteolytic arthritis and direct inhibition of this transcription factor by unique and novel I-kappaB mutant proteins blocks manifestation of the disease...

..In this issue of Cell Stem Cell, Wu et al. (2010) demonstrate that this event is mediated by osteoclastic mobilization of active transforming growth factor β1, which is inhibited by a common antiosteoporosis drug...

..In this issue of Cell, Lee et al. (2007) demonstrate in mice that bone regulates the insulin/glucose axis and energy metabolism, providing a new framework for approaching common disorders of bioenergetics...